GB2252951A

GB2252951A - Packaging freeze dried vaccine in syringes

Info

Publication number: GB2252951A
Application number: GB9203196A
Authority: GB
Inventors: Michel Germain Henri Galy; Alain Gomez
Original assignee: Pasteur Merieux Serum et Vaccines SA
Current assignee: Sanofi Pasteur SA
Priority date: 1991-02-15
Filing date: 1992-02-14
Publication date: 1992-08-26
Anticipated expiration: 2012-02-14
Also published as: CA2061204A1; GB2252951B; BE1007303A4; GB9203196D0; FR2672868A1; CA2061204C; DE4204309A1; FR2672868B1; US5184450A

Abstract

In a method of packaging freeze dried vaccine in a bypass syringe the sterilized syringes are disposed in rows in an aseptic dispensing machine. Doses 23 of the solution or suspension to be freeze dried are introduced into the syringes. A temporary plug 11 is inserted in the same machine into the mouth of the syringe body in a first position allowing communication between the interior of the syringe body and the exterior. The syringes are introduced into a freeze drying machine and the vaccine is freeze dried. At the end of the freeze drying cycle the temporary plug 11 is depressed in a controlled atmosphere in the tank of the freeze drying machine into a hermetic sealing position (Figure 8d). The syringes are transferred into an aseptic dispensing machine. The temporary plug 11 is removed, an intermediate piston-plug 9 is fitted, a dose 25 of solvent is introduced and an end piston-plug 10 is fitted. The temporary plug preferably comprises a ribbed first part (12, 13, Figure 5), which enters the syringe in the first plug position, a second part with a sealing annular rib (1, 8, Fig. 5) and a third handling part above a shoulder which determines the maximum insertion of the plug. The third part may have a groove 21 to co-operate with a grasping tool. <IMAGE>

Description

1 1 7' 1---. 1 2

SPECIFICATION

Method of Packagina freeze dried vaccines in svrinaes and -plucr f or implementing the method The present invention concerns a method of packaging freeze dried vaccines in syringes and a plug for implementing the method.

So-called bypass syringes designed to contain a freeze dried active substance and a solvent are already known. Generally made from glass, these syringes have a generally cylindrical syringe body with a passage leading to the needle in the anterior part and a piston-plug in the posterior part coupled to a piston rod actuated by the user. The cylindrical cavity inside the body is divided into two parts, namely an anterior part containing the freeze dried active substance and a posterior part separated from the anterior part by an intermediate piston- plug and containing the solvent. A bypass is provided by a localized longitudinal rib in the glass. In an initial position the bypass communicates with the anterior part containing the freeze dried active substance and is inaccessible to the liquid because of the presence of the intermediate piston-plug. When the user depresses the end iston-plug the liquid depresses the intermediate piston-plug until it uncovers the bypass whereupon the liquid is expelled into the first part containing the freeze dried active substance. The dissolved active substance is expelled from the syringe through the needle after the two pisto ns come into contact.

However, these syringes are not generally used for freeze dried vaccines because these vaccines are extremely fragile, very sensitive to the relative humidity and temperature of their surroundings, so that it is not possible to carry out under industrial conditions in situ freeze drying in a freeze drying aachine followed by fitting of the intermediate piston-plug and filling in a second, so-called dispensing machine because of the breakdown in the continuity of the environment. As a result freeze dried vaccines such as the particularly fragile Haemophilus vaccine, for example, must be packaged in syringes with no solvent so that the medical or nursing personnel must first draw up the solvent from a bottle.

The present invention proposes to remedy these drawbacks and to enable the packaging of fragile freeze dried vaccines in bypass syringes without compromising the quality of the vaccine.

Another objective of the invention is to implement this process using conventional freeze drying installations and conventional dispensing installations or installations which require only minor and temporary modification.

Thus according to one aspect of the present invention there is provided a method of packaging freeze dried vaccine in a bypass syringe with a solvent comprising:

(I) dosing a syringe with a vaccine in an aseptic dosing machine; (ii) transferring said dosed syringe to a freeze drying machine and freeze drying said vaccine; and (III) transferring said dosed syringe to an aseptic dosing machine In a hermetically sealed state, fitting an intermediate piston-plug and dosing said syringe with a solvent; wherein said syringe is fitted with a temporary, multipositional plug allowing in a first position communication between the interior of said syringe and the exterior, and in a second position, the hermetic-sealing of said syringe, the plug being disposed into the second position after the freeze drying step.

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- 3 1 In accordance with a second aspect of the Invention there is provided a method of packaging freeze dried vaccine in a bypass syringe in which sterilized syringes are disposed in rows in an aseptic dispensing machine, doses of a solution or suspension to be freeze dried are introduced into said syringes, a temporary plug is inserted in the same machine into the mouth of said syringe body in a position allowing communication between the interior of said syringe body and the exterior, said syringes are introduced into a freeze drying machine, the vaccine is freeze dried, at the end of the freeze drying cycle said temporary plug is depressed in a controlled. atmosphere in said freeze drying machine into a hermetic sealing position, said syringes are transferred into an aseptic dispensing machine,, said temporary plug is removed, an intermediate piston-plug is fitted, the dose of solvent Is introduced and an end terminal piston-plug is fitted. In the first phase of the process, in the laminar is -h-- flow aseptic dispensing area of machine supplied with groups- of special strips or cassettes, the the first dispensing syringes disposed in solution or suspension into the syringes after fitted either in the to be freeze dried is dispensed which the temporary plugs are machine or using another device. The temporary plugs can be inserted to the position allowing freeze drying- using conventional methods.

After the cassettes of syringes are transferred into the freeze drying machine and freeze drying has been carried out the temporary plug is depressed in a controlled atmosphere in the freeze drying machine by simple displacemenp of a plate so that the closure is hermetically sealed although part of the temporary plug projects externally to allow cooperation with grasping means enabling it to be extracted in the aseptic dispensing area in which the automatic solvent dispensing k machine is located.

The process has the further advantage of enabling syringes containing the freeze dried vaccine to be stored for as long as necessary before the solvent is added.

The temporary plug can be any suitable shape, preferably comprising three consecutive parts, namely a first part entering at least partially into the syringe body leaving passages enabling communication between the interior of the syringe and the exterior environment, a second part adapted to be inserted into the syringe body in a second insertion position of the plug to achieve hermetic sealing of the syringe body and a third part preferably projecting to the exterior in any position of the plug enabling the plug to be grasped and withdrawn from the syringe body.

In a preferred embodiment th-- temporary plug advantageously comprises three (for example) longitudinal ribs in said first part leaving between them passages for 1 vapour and gas, the second part comprising a peripheral sealing rib or lip and the third part having means such as a peripheral groove enabling it to be grasped by an extractor tool.

The first part of the plug advantageously. has an intermediate abutment relief portion enabling accurate positioning in the part-inserted freeze drying position, the abutment being sufficiently flexible to allow further insertion of the plug when a greater force is exerted.

In a second aspect, the present invention consists in a temporary plug for implementing a method of packaging freeze dried vaccine in a bypass syringe in which sterilized pyringes are disposed in rows in an aseptic dispensing machine, doses of a solution or suspension to be freeze dried are introduced into said syringes, a temporary plug is inserted in the same machine into the mouth of said syringe body in a position allowing communication between the interior of said syringe body and the exterior, said syringes are introduced into a freeze drying machine,, the vaccine is freeze dried, at the end of the freeze drying cycle said temporary plug is depressed in a controlled atmosphere in said freeze drying machine into a hermetic sealing position, said syringes are transferred into an aseptic dispensing machine, said temporary plug is removed, - an intermediate piston-plug is fitted, the dose of solvent is introduced and an end terminal piston-plug is fitted, said temporary plug comprising a first part adapted to enter at least partially-into said syringe body and said passages enabling communication between the interior of said syringe and the exterior environment, a second part adapted to be inserted into said syringe body in a second insertion position of said temporary plug to seal hermetically said syringe body, and a third part adapted to project to the outside in any position of said temporary plug to enable grasping of said temporary plug to remove it from said syringe body.

According to a third aspect of the invention there are provided bypass syringes containing a vaccine and a solvent packaged according to the method as described above.

Other advantages and features of the invention will emerge from the following description given by way of non-limiting example only with reference to the appended.drawings, in which:

- figure 1 is a view in elevation of a bypass syringe body, - figures 2, 3 and 4 are views in elevation and partially in cross- section of an end plug adapted to be fitted to the end of the syringe adapted to receive the needle, an intermediate o3z bypass plug and an end piston-plug, - figure 5 is a view in elevation of a temporary plug in accordance with the invention, - figures 6 and 7 show the plug in cross-section on the lines VI-V1 and VII-VII in figure 5, - figure 8 is a diagram showing four stages of the method, stages 8a and 8b being carried out in a first or dispensing area and stages 8p and 8d in the freeze drying machine, figure 9 is a diagram showing four consecutive stages in a second or solvent dispensing area.

Referring to all the figures:

According to the invention, freeze dried vaccine (Haemophilus vaccine, for example) is packaged in bypass syringes. Figure 1 shows a bypass syringe made from glass and having a body 1 having at the front an end- piece 2 adapted to receive the needle and at the rear a conventional shoulder 3, the mouth 4 of the cylindrical internal cavity 5 having a peripheral lip forming a conventional small rib which very slightly reduces the diameter of the mouth 4 relative to the diameter of the cylindrical internal cavity 5. Approximately one third of the way in from the front end, a relatively short longitudinal rib 6 is blown whose inside forms a longitudinal bypass groove 7. Syringes of this design are available through ordinary trade channels.

The end plug 8 is f itted over the end-piece 2 to close of f the passage in the end-piece and to seal the syringe at this end.

The bypass piston-plug.9 shown in f igure 3 is also of a conventional type and is designed to separate the f reeze dried vaccine in the anterior part of the body 5 f rom the solvent in the posterior part, tle plug 9 sealing the rear end of the bypass 7 between the anterior part that it delimits and which contains the freeze dried vaccine and the pQsterior part containing the solvent. Finally,.the end piton 10 is also of a conventional type is and. as shown in figure 4, includes a screwthreaded posterior cavity into which a piston rod (not shown) can be screwed.

Referring to figures 5 through 7, the temporary plug 11 is divided lengthwise into three functional parts.

The first is a small diameter generally cylindrical part 12 upstanding from which are three substantially cylindrical crosssection columns 13 whose ends 14 are slightly bevelled to facilitate. insertion into the mouth of the syringe. These columns or ribs 13 are -slightly thicker at their upper end 15 to form small shoulders 16 acting as abutments to determine an intermediate position of the plug 11. Above the part 15 of the columns 13 the plug has a frustoconical divergent portion 17 ending in a peripheral sealing rib 18. The overall radial dimension of the columns 13 is substantially equal to---the diameter of the cavity 5 or of the mouth 4 so that the plug can be inserted with slight friction into 'the mouth. The diameter of the part 15 of the columns is slightly greater than the diameter of the mouth.4 so as to form an 4 abutment and to determine a semi-inserted position in which the columns 12 are inside the syringe body while their part 15 remains outside so that a passage for gas and vapour between the interior of the syringe body and the surrounding environment is provided at the surfaces 12 and 17. The diameter of the rib 18 is sufficiently larger than the diameter of the mouth 4 and the cavity 5 that, when the plug is inserted further, the rib 18 provides a perfect seal at the mouth.

A part 19 of reduced diameter lies above the sealing rib 18. Above this the third.-part of the plug determining the maximum Above the shoulder 20 is a gcove 21 adapted to cooperate with a grasping tool which is used to extract the plug which is inserted by applying pressure to its upper end 22.

Referring to figures 8 and 9:

This method in accordance with the invention of packaging the vaccine begins with washing, coating with silicone and autoclaving the plugs 9 and 10. The plugs 8 and 11 are also washed and then sterilized. On a conventional automated preparation machine the syringe bodies are disposed in series of 18 on compartmented strips after which the end plug 8 is automatically fitted. The next stage, also conventional, is to wash and coat with silicone.the interior body of- the syringes which are grouped together and then stowed in special cassettes which are then sterilized in the autoclave.

The sterilized cassettes are brought to a conventional laminar flow aseptic dispensing area and in stage 8a the various syringes in the cassette receive'the dose 23 of liquid vaccine in a conventional dispensing machine. After the dose is dispensed -into each syringe in the cassette the machine fits a temporary plug 11 to each syringe and inserts it until the shoulders 16 come features a wide shoulder insertion of the plug into the syringe body.

19.1- is into contact with the lip at the mouth so that insertion is limited and passages are left between the interior of the syringe body 5 and the exterior. The cassettes are then moved into the freeze drying machine. During the first stage Sc in the freeze drying machine freeze drying is carried out to produce the freeze dried vaccine 24. At the end of freeze drying, in stage 8d, the freeze drying machine plate is moved slightly so that the temporary plug 11 is depressed until the sealing rib 18 enters the body and seals it. The cassettes of syringes can then be taken out of the f reeze drying machine and transported without requiring special precautions. In this condition they can be stored for long periods.

The cassettes containing the. syringes with the freeze dried vaccine protected in this way are then taken to a second laminar flow aseptic dispensing area in which the temporary plugs 11 are extracted in stage ga, optionally for recovery and recycling. To this end the machine may advantageously comprise forked fingers which are inserted into the groove 21 to remove the plug. Stage 9b, also carried out in this conventional machine, depresses the bypass piston plug to its position above the upper end of the bypass 6, thereby isolating the ante rior part which contains the freeze dried vaccine 24.

The dispensing machine then introduces into each syringe the dose 25 of solvent (stage 9p.) after-which (stage 9d) the end piston-plug 10 is fitted to complete the packaging process.

Although the invention has been described with reference to a specific embodiment, it is no way limited thereto. of course, and various modifications of shape or materials may be made thereto without departing from the scope or spirit of the invention.

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Claims

1. A method of packaging freeze d2:d-ed vaccine in a bypass syringe with a solvent ccnp=ing:

(i) dosing a syringe with a vaccine in an aseptic dosing machine; (JJ), transferring said dosed syringe to a freeze drying machine and freeze diyirxj said vaccine; and (iu)transferring said dosed syringe to an aseptic dosing machine in a hiermetically sealed state, fitting an intermediate piston-plug and dosing said syringe with a solvent; whe said syringe is fitted with a t, multipositional plug allowing in a first posItien communication between the interior of said syringe and the exterior, and in..a sec=,d position, the hermetic sealing of said syringe, the plug being disposed into the second position after the freez.-- drying step.

2. A method of packaging freeze dried vaccine in a bypass syringe in which sterilized syringes are disposed in row in an aseptic dispensing machine, doses of a solution or suspension to be freeze dried are introduced into the syrimes, a temporary plug is inserted in the same macl-dne into the mouth of the syrime body:in a position allowing ccarmriicatien between the interior of the syringe body and the exterior, the syringes are - into a freeze drying machine, the vaccine is freeze dried, at the end of the freeze drying cycle the temporary plug is depressed In a controlled atmosphere in the tank of the freeze drying machine into a hermetic sealing position, the syringes are transferred into an aseptic dispensing machine, the temporary plug is ren, an intermediate piston-plug is fitted, tl-p- dose of solvent is introduced and an ex)d piston-plug is fitted.

3. A method according to Claim 1 wherein, said syringe is fittted wIth an end pistcn-plug m letion of said method.

4. A method according to any of Claim 1 to 3 wherein the tempacary plug is depressed in a controlled in the tank of the fteeze drying machine by moving a plate of the freeze drying machine.

5. A mthod according to any preceding claim wherein the temporary plug is extracted in a lamx= flaw aseptic dispensing machine by mews of forked fingers.

6. A method according to any Preceding claim whexei-n the teMPOrarY plugs are recycled.

7. A method according to any preceding claim wherein said vaccinie, is a fragile vaccine.

8. A mtlr)d according to any preceding claim whe said vaccine is Haemophilus vaccine.

9. A trary plug for use in Packaging freeze dried vaccine In a bypass syringe, said trary plug comprising a first part adapted to enter at least partially into the syringe body in a first position leaving passages enabling cccnmuriicaticn between the interior of the syr and the exterior environment, a second part adapted to be inserted into the syringe body in a second position to seal hermietically the syringe body, and a tId-rd part adapted to project to the outside In arry position of the temporary plug to enable grasping of the trary plug to remove it from the syringe body.

10. A plug according to Claim 9 further rising on said first part a plurality of ribs between which are passages for vapour and gas.

11. A plug according to Claim 9 or Claim 10 wherein said first part has a small shoulder whereby the temporary plug may be positioned initially in the syringe body.

12. A plug according to any of Claims 9 to 11 wherein said sw=rd part has a peripheral rib or lip.

13. A plug according to any of Claims 9 to 12 Wherein said third part has a peripheral groove enabling it to be grasped by an extractor tool.

14. A bypass syringe containing a vaccwi-- and a solvent packaged according to a method as claimed in any of Claiim 1 to 8.

15. A method of packaging freeze dried vaccine in a bypass syringe substantially as hereinbefore described wIth reference to any one of the 1 acc,:xLp&Wing drawings.

16. A temporary plug substantially as hereirlefc)re described With reference to any one of the acocinparying drawings.